Process for production of optically active allyl compound

ABSTRACT

To provide a novel process for producing an optically active allyl compound which is useful as an intermediate raw material for e.g. pharmaceutical products. 
     A process for producing an optically active allyl compound of the formula (4): 
     
       
         
         
             
             
         
       
     
     (wherein “*” represents an asymmetric carbon atom), which comprises reacting an allyloxy compound of the formula (1): 
     
       
         
         
             
             
         
       
     
     (wherein R 1  is a C 1-6  alkyl group or a C 1-6  alkoxyl group, and each of R 2 , R 3 , R 4 , R 5  and R 6  independently is a C 1-6  alkyl group which may be linear, branched or cyclic, a hydrogen atom or a C 6-12  aromatic group, provided that R 2  and R 6  may be located in the same ring) with a hydrogenated compound of the formula (3): 
     
       
         
         
             
             
         
       
     
     (wherein X is a carbon atom, an oxygen atom, a sulfur atom or a nitrogen atom, and each of R 8 , R 9  and R 10  independently is a C 1-24  alkyl group which may be linear, branched or cyclic, a C 1-24  alkylcarbonyl group which may be branched or cyclic, a C 1-24  alkoxycarbonyl group which may be branched or cyclic, a hydrogen atom, a halogen atom or a C 6-10  aromatic group, or two of R 8 , R 9  and R 10  may together form a ring containing one or two carbonyl groups), in the presence of a palladium compound and an optically active phosphine ligand of the formula (2): 
     
       
         
         
             
             
         
       
     
     (wherein each of Ar 1 , Ar 2 , Ar 3  and Ar 4  independently is a C 6-10  aromatic group, and R 7  is a structure having at least one asymmetric center or axial chirality), wherein a tertiary amine of the formula (5): 
     
       
         
         
             
             
         
       
     
     (wherein each of R 11 , R 12  and R 13  independently is a C 2-12  aliphatic group or a C 2-12  substituted aliphatic group, which may be linear, branched or cyclic, or a C 6-10  aromatic group or a C 6-10  substituted aromatic group) is present in the above reaction system.

TECHNICAL FIELD

In a process for producing an optically active allyl compound, thepresent invention provides a novel process which is excellent inoperation efficiency, can be operated at low cost, and has high opticalselectivity.

BACKGROUND ART

A process for producing an optically active allyl compound has beendesired, and specifically, an asymmetric synthetic reaction using acatalyst made of a combination of a palladium compound and an opticallyactive phosphine ligand, has been actively studied (e.g. Non-patentDocument 1). With respect to using a base as a reaction reagent, (1) amethod of using sodium hydride, (2) a method of usingN,O-bis(trimethylsillyl)acetamide (e.g. Non-patent Document 1), (3) amethod of using cesium carbonate (e.g. Non-patent Document 2) and (4) amethod of using sodium hydride and a halogenated quaternary ammoniumsalt (e.g. Non-patent Document 3), are known.

Non-patent Document 1: Chemical Review, Vol. 103, p. 2921 (2003)

Non-patent Document 2: Angewandte Chemie International Edition inEnglish, Vol. 35, p. 100 (1996)

Non-patent Document 3: Journal of the American Chemical Society, Vol.116, p. 4089 (1994)

DISCLOSURE OF THE INVENTION Problems to be Solved by the Invention

However, the above methods had the following problems respectively,whereby it was difficult to practice a mass production.

(1) With respect to the method of using sodium hydride, the reactionsystem tends to be gelled, so that stirring will become impossible.Further, the optical purity of an optically active allyl compound as theproduct, is low.

(2) With respect to the method of usingN,O-bis(trimethylsillyl)acetamide, the reagent is expensive. Further,the optical purity of an optically active allyl compound as the product,is low.

(3) With respect to the method of using cesium carbonate, the reagent isexpensive. Further, the reaction solution becomes a slurry, and a solidprecipitates, whereby it is difficult to withdraw it during a massproduction.

(4) With respect to the method of using sodium hydride and a halogenatedquaternary ammonium salt, the reaction system tends to be gelled, sothat stirring will become impossible. Further, the reagent is expensive.Furthermore, reproductivity of the reaction is low, and the opticalpurity of an optically active allyl compound as the product, fluctuates.

Therefore, it has been desired to develop a novel process which isexcellent in operation efficiency, can be operated at low cost, and hashigh optical selectivity, which are difficult to attain by theconventional methods.

Means to Solve the Problems

The present inventors have conducted extensive studies to overcome theabove problems, and as a result, they have found that by using atertiary amine, the above problems can be solved. The present inventionhas been accomplished on the basis of the discovery.

Namely, the present invention provides the following.

(1) A process for producing an optically active allyl compound of theformula (4):

(wherein “*” represents an asymmetric carbon atom), which comprisesreacting an allyloxy compound of the formula (1):

(wherein R¹ is a C₁₋₆ alkyl group or a C₁₋₆ alkoxyl group, and each ofR², R³, R⁴, R⁵ and R⁶ independently is a C₁₋₆ alkyl group which may belinear, branched or cyclic, a hydrogen atom or a C₆₋₁₂ aromatic group,provided that R² and R⁶ may be located in the same ring) with ahydrogenated compound of the formula (3):

(wherein X is a carbon atom, an oxygen atom, a sulfur atom or a nitrogenatom, and each of R⁸, R⁹ and R¹⁰ independently is a C₁₋₂₄ alkyl groupwhich may be linear, branched or cyclic, a C₁₋₂₄ alkylcarbonyl groupwhich may be branched or cyclic, a C₁₋₂₄ alkoxycarbonyl group which maybe branched or cyclic, a hydrogen atom, a halogen is atom or a C₆₋₁₀aromatic group, or two of R⁸, R⁹ and R¹⁰ may together form a ringcontaining one or two carbonyl groups), in the presence of a palladiumcompound and an optically active phosphine ligand of the formula (2):

(wherein each of Ar¹, Ar², Ar³ and Ar⁴ independently is a C₆₋₁₀ aromaticgroup, and R⁷ is a structure having at least one asymmetric center oraxial chirality), wherein a tertiary amine of the formula (5):

(wherein each of R¹¹, R¹² and R¹³ independently is a C₂₋₁₂ aliphaticgroup or a C₂₋₁₂ substituted aliphatic group, which may be linear,branched or cyclic, or a C₆₋₁₀ aromatic group or a C₆₋₁₀ substitutedaromatic group) is present in the above reaction system.(2) The process according to the above (1), wherein the optically activephosphine ligand is a compound of the formula (6):

(3) The process according to the above (1), wherein the optically activephosphine ligand is a compound of the formula (7):

(4) The process according to the above (1), wherein the allyloxycompound is cyclopentenyl acetate of the formula (8):

(5) The process according to the above (1), wherein the allyloxycompound is a compound of the formula (9):

(6) The process according to the above (1), wherein the tertiary amineis tri-n-propylamine.(7) The process according to the above (1), wherein the tertiary amineis tri-n-octylamine.(8) The process according to the above (1), wherein the tertiary amineis diisopropylethylamine.(9) The process according to the above (4), wherein the hydrogenatedcompound is a compound of the formula (10):

(10) The process according to the above (1), wherein the hydrogenatedcompound has a pKa of at most 16 in water.

BEST MODE FOR CARRYING OUT THE INVENTION

Now, the present invention will be described in further detail. In thedefinitions of the compounds in the present specification, for example,“C₁₋₆” means having from 1 to 6 carbon atoms, and “C₁₋₂₄”, “C₂₋₁₂”,“C₆₋₁₂”, “C₆₋₁₀”, etc. have the corresponding meanings, respectively.

As shown in the above reaction scheme, in the present invention, in asolvent, an optically active phosphine ligand of the formula (2) and apalladium compound are added to an allyloxy compound of the formula (1),and a hydrogenated compound of the formula (3) and a tertiary amine ofthe formula (5) are further added thereto, whereby it is possible toproduce an optically active allyl compound of the formula (4).

As the allyloxy compound of the formula (1), it is possible to useeither an optically active form or a racemic modification. It may, forexample, be cyclopentenyl acetate, diphenylallyl acetate orcyclopentenylmethyl carbonate.

The optically active phosphine ligand of the formula (2) may, forexample, be1,2-diaminocyclohexane-N,N′-bis(2′-diphenylphosphinobenzoyl),1,2-diaminocyclohexane-N,N′-bis(2′-diphenylphosphinonaphthoyl),1,2-diaminodiphenylethane-N,N′-bis(2′-diphenylphosphinobenzoyl),2,2′-bis(diphenylphosphino)-1,1′-binaphthyl or2,2′-bis(di(3,5-xylyl)phosphino)-1,1′-binaphthyl.

Further, the absolute configuration of the product is determined by theabsolute steric configuration of the optically active phosphine ligand.For example, when the optically active phosphine ligand is(S,S)-1,2-diaminocyclohexane-N,N′-bis(2′-diphenylphosphino benzoyl),(S,S)-1,2-diaminocyclohexane-N,N′-bis(2′-diphenylphosphinonaphthoyl),(S,S)-1,2-diaminodiphenyl ethane-N,N′-bis(2′-diphenylphosphinobenzoyl),(R)-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl or(R)-2,2′-bis(di(3,5-xylyl)phosphino)-1,1′-binaphthyl, an R-configurationis obtainable.

The amount of the optically active phosphine ligand to be used, isusually within a range of from 0.001 to 1 mol equivalent, preferablyfrom 0.002 to 0.1 mol equivalent, based on 1 mol equivalent of theallyloxy compound.

The above palladium compound may, for example, be palladium chloride,palladium acetate, dichlorobis(triphenylphosphine)palladium,tetrakis(triphenylphosphine)palladium,di-μ-chlorobis[(η-allyl)palladium], bis[(acetylacetonate)palladium],dichlorobis[(benzonitrile)palladium], palladium propionate,tris(dibenzylidene acetone)dipalladium or[1,1′-bis(diphenylphosphino)ferrocene]palladium chloride. Among them,dichlorobis(triphenylphosphine)palladium,di-μ-chlorobis[(η-allyl)palladium] and tris(dibenzylideneacetone)dipalladium are preferred.

The amount of the palladium compound to be used is usually within arange of from 0.1 to 3 mol equivalent, preferably from 0.9 to 1.2 molequivalent, based on 1 mol equivalent of the optically active phosphineligand. It is considered that such an optically active phosphine ligandforms a catalyst by coexisting with the above palladium compound.

With respect to the hydrogenated compound of the formula (3), the lowerthe acid dissociation constant (pKa) of hydrogen at the reaction point,in water, the higher the reaction rate, and pKa is preferably at most16, more preferably at most 13. Such a hydrogenated compound may, forexample, be an ester such as dimethyl malonate, diethyl malonate, ethylacetoacetate, ethyl 2-fluoroacetoacetate, ethyl nitroacetate or ethylfluoroacetate; a diketone such as acetylacetone; a nitrile such asmolononitrile or ethyl cyanoacetate; a nitro compound such asnitromethane or nitroethane; an imide such as succinic imide or phthalicimide; a secondary amine such as diethylamine or dibenzylamine; or athioacetic acid.

The amount of the hydrogenated compound to be used is usually within arange of from 0.1 to 3 mol equivalent, preferably from 0.9 to 1.2 molequivalent, based on the allyloxy compound.

As the tertiary amine of the formula (5), it is possible to use anoptional tertiary amine. In the formula (5), each of R¹¹, R¹² and R¹³independently may be a C₂₋₁₂ aliphatic group (e.g. a hydrocarbon groupsuch as an alkyl group, or a hydrocarbon group containing an unsaturatedbond such as an allyl group) or a C₂₋₁₂ substituted aliphatic group(e.g. a substituted hydrocarbon group such as a benzyl group or aphenethyl group), which may be linear, branched or cyclic, or a C₆₋₁₀aromatic group (such as a phenyl group or a naphthyl group) or a C₆₋₁₀substituted aromatic group (such as a tolyl group or a xylyl group). Thetertiary amine may, preferably, be a linear alkylamine such astriethylamine, tripropylamine, tributylamine, tripentylamine ortrioctylamine; a branched alkylamine such as diisopropylethylamine; ananiline such as dimethyl aniline; a benzylamine such as dimethylbenzylamine, an allylamine such as triallylamine, a diamine such astetramethyl ethylene diamine or an alicyclic amine such as1,8-diazabicyclo[5.4.0]-7-undecene (DBU).

The amount of the tertiary amine to be used, is not particularly limitedas long as it is the amount which does not interrupt the reaction anddoes not cause a side reaction. However, the amount is usually within arange of from 0.1 to 10 mol equivalent, preferably from 0.5 to 5 molequivalent, more preferably from 0.9 to 1.1 mol equivalent, based on thehydrogenated compound.

The order of adding the allyloxy compound, the optically activephosphine ligand, the palladium compound, the hydrogenated compound andthe tertiary amine, may be changed in any order, but it is preferred todropwise add a mixture of the hydrogenated compound and the tertiaryamine to a mixture of the optically active phosphine ligand, thepalladium compound and the allyloxy compound.

The present reaction may be carried out without any solvent, butusually, it is preferred to use a solvent for the reaction.

As the solvent, water or an organic solvent is used, but it is notparticularly limited as long as it is stable under the reactionconditions, and it does not interrupt the objective reaction. It ispossible to use, for example, an alcohol (such as ethanol, propanol,butanol or octanol), a cellosolve (such as methoxyethanol orethoxyethanol), an aprotic polar organic solvent (such as dimethylformamide, dimethyl sulfoxide, dimethyl acetamide, tetramethyl urea,sulfolane, N-methyl pyrrolidone or N,N-dimethyl imidazolidinone), anether (such as diethyl ether, diisopropyl ether, t-butyl methyl ether,tetrahydrofuran or dioxane), an aliphatic hydrocarbon (such as pentane,hexane, c-hexane, octane, decane, decalin or petroleum ether), anaromatic hydrocarbon (such as benzene, chlorobenzene, o-dichlorobenzene,nitrobenzene, toluene, xylene, mesitylene or tetralin), a halogenatedhydrocarbon (such as chloroform, dichloromethane, dichloroethane orcarbon tetrachloride), a ketone (such as acetone, methyl ethyl ketone,methyl butyl ketone or methyl isobutyl ketone), a low aliphatic acidester (such as methyl acetate, ethyl acetate, butyl acetate or methylpropionate), an alkoxyalkane (such as dimethoxyethane or diethoxyethane)or a nitrile (such as acetonitrile, propionitrile or butylonitrile).

The above solvents may be used alone or in combination as a mixture oftwo or more of them.

Further, it is possible to use such a solvent as a nonaqueous solvent byusing a proper dehydrating agent or a desiccant, as the case requires.

The optical purity of the optically active allyl compound as the productdepends on the type of a solvent. The preferred solvent may, forexample, be a halogenated hydrocarbon, but other than that, a preferredsolvent may exist.

The amount of the reaction solvent to be used, is usually within a rangeof from 1 to 200 times by weight more preferably from 3 to 10 times byweight, based on the allyloxy compound.

The reaction temperature is possibly be at from −100° C. to the boilingpoint of the solvent to be used, but it is preferably from −50° C. to50° C., more preferably from −10° C. to 20° C.

The reaction time varies depending on the reaction temperature and thepKa of the hydrogenated compound, and it may not simply be determined.However, in a case where the reaction temperature is 0° C. and the pKaof the hydrogenated compound is 10, it is enough to carry out thereaction for 1 hour.

After the reaction, water is added, followed by extraction with a propersolvent, and the solvent is concentrated under reduced pressure toisolate the desired optically active allyl compound. It is possible toisolate the highly purified optically active allyl compound bypurification such as recrystallization, distillation or silica gelcolumn chromatography, as the case requires.

Further, from the viewpoint of operation safety, it is preferred tocarry out the reaction in an atmosphere of an inert gas such asnitrogen, argon or helium.

EXAMPLES

Now, the present invention will be described in further detail withreference to Examples, but the present invention is by no meansrestricted by the following Examples.

Examples 1 to 11

Into a glass reactor which was flushed with nitrogen, 0.47 mmol of anoptically active phosphine ligand and 0.20 mmol ofdi-μ-chlorobis[(η-allyl)palladium] were put, and 5 g of methylenechloride was added to dissolve them. Then, 7.9 mmol of an allyloxycompound was added, followed by stirring at 0° C. for 10 minutes. On theother hand, into another glass reactor which was flushed with nitrogen,7.9 mmol of a hydrogenated compound and 7.9 mmol of a tertiary aminewere put, and 3 g of methylene chloride was added to dissolve them. Thesolution at that time was visually observed if it was gelled. The abovetwo solutions were mixed at 0° C., followed by a reaction for one hour.5 g of water was added to the reaction solution, followed by stirring,and then, the solution was subjected to liquid separation. The organicphase was concentrated under reduced pressure. The concentrated liquidwas purified by silica gel column chromatography (silica gel: 30 g,developing solution: hexane/ethyl acetate=80/20), to obtain an opticallyactive allyl compound. A part of the product was used for HPLC analysisusing an optically active column, to determine the optical purity.

Comparative Examples 1 to 4

Into a glass reactor which was flushed with nitrogen, 0.47 mmol of anoptically active phosphine ligand and 0.20 mmol ofdi-μ-chlorobis[(η-allyl)palladium] were put, and 5 g of methylenechloride was added to dissolve them. Then, 7.9 mmol of an allyloxycompound was added, followed by stirring at 0° C. for 10 minutes. On theother hand, into another glass reactor which was flushed with nitrogen,7.9 mmol of a hydrogenated compound was put, and 3 g of methylenechloride was added to dissolve it. 7.9 mmol of a base was added thereto.The solution at that time was visually observed if it was gelled. Theabove two solutions were mixed at 0° C., followed by a reaction for onehour. 5 g of water was added to the reaction solution, followed bystirring, and then, the solution was subjected to liquid separation. Theorganic phase was concentrated under reduced pressure. The concentratedliquid was purified by silica gel column chromatography (silica gel: 30g, developing solution: hexane/ethyl acetate=80/20), to obtain anoptically active allyl compound. A part of the product was used for HPLCanalysis using an optically active column, to determine the opticalpurity.

Comparative Example 5

Into a glass reactor which was flushed with nitrogen, 0.47 mmol of anoptically active phosphine ligand and 0.20 mmol ofdi-μ-chlorobis[(η-allyl)palladium] were put, and 5 g of methylenechloride was added to dissolve them. Then, 7.9 mmol of an allyloxycompound was added, followed by stirring at 0° C. for 10 minutes. On theother hand, into another glass reactor which was flushed with nitrogen,7.9 mmol of a hydrogenated compound was put, and 3 g of methylenechloride was added to dissolve it. 7.9 mmol of sodium hydride was addedthereto. The solution at that time was visually observed if it wasgelled. 7.9 mmol of tetra-n-hexylammonium bromide was added to thesolution. The above two solutions were mixed at 0° C., followed by areaction for one hour. 5 g of water was added to the reaction solution,followed by stirring, and then, the solution was subjected to liquidseparation. The organic phase was concentrated under reduced pressure.The concentrated liquid was purified by silica gel column chromatography(silica gel: 30 g, developing solution: hexane/ethyl acetate=80/20), toobtain an optically active allyl compound. A part of the product wasused for HPLC analysis using an optically active column, to determinethe optical purity.

The results of Examples and Comparative Examples are shown in Tables 1and 2. Further, in Tables, Et represents an ethyl group, n-Pr a n-propylgroup, I-Pr an isopropyl group, c-Pr a cyclopropyl group, n-Bu a n-butylgroup, s-Bu a secondary butyl group, i-Bu an isobutyl group, t-Bu atertiary butyl group, c-Bu a cyclobutyl group, n-Pen a n-pentyl group,c-Pen a cyclopentyl group, n-Hex a n-hexyl group, c-Hex a cyclohexylgroup, Hep a heptyl group, Oc an octyl group, and Ph a phenyl group.Further, structural formulae corresponding to numbers in Tables, are asfollows.

TABLE 1 Optically Steric Hydroge- active Optical configu- Allyloxy natedallyl Yield purity ration Example compound Ligand compound Base Gelationcompound (%) (% ee) (R/S) 1 (1)-1 (2)-1 (3)-1 n-Pr₃N None (8)-1 15 97 R2 (1)-1 (2)-1 (3)-2 n-Pr₃N None (8)-2 48 99 R 3 (1)-1 (2)-1 (3)-3 n-Pr₃NNone (8)-3 94 95 R 4 (1)-1 (2)-1 (3)-4 n-Pr₃N None (8)-4 88 100 R 5(1)-1 (2)-1 (3)-5 n-Pr₃N None (8)-5 92 92 R 6 (1)-1 (2)-1 (3)-6 n-Pr₃NNone (8)-6 92 98 R 7 (1)-1 (2)-1 (3)-6 Et₃N None (8)-6 90 92 R 8 (1)-1(2)-1 (3)-6 n-Oc₃N None (8)-6 92 99 R 9 (1)-1 (2)-1 (3)-6 i-Pr₂EtN None(8)-6 98 98 R 10 (1)-2 (2)-1 (3)-4 n-Pr₃N None (9)-4 90 100 R 11 (1)-2(2)-2 (3)-4 n-Pr₃N None (9)-4 90 90 R

TABLE 2 Optically Steric Compara- Hydroge- active Optical configu- tiveAllyloxy nated allyl Yield purity ration Example compound Ligandcompound Base Gelation compound (%) (% ee) (R/S) 1 (1)-1 (2)-1 (3)-6 NaHObserved (8)-6 65 50 R 2 (1)-1 (2)-1 (3)-5 *1 None (8)-5 94 85 R 3 (1)-2(2)-2 (3)-4 *1 None (9)-4 90 86 R 4 (1)-1 (2)-1 (3)-4 Cs₂CO₃ Slurry(8)-4 80 100 R 5 (1)-1 (2)-1 (3)-6 *2 None (8)-6 87 92 R *1:N,O-bis(trimethylsilyl)acetamide *2: NaH/n-Hex₄NBr

By comparing Examples 6 to 9 with Comparative Example 1, it is evidentthat with the process using the tertiary amine of the present invention,the reaction system does not become gelled, and the obtainable opticallyactive ally compound has a high optical purity.

By comparing Example 5 with Comparative Example 2, it is evident thatwith the process using the tertiary amine of the present invention, theobtainable optically active ally compound has a high optical purity.

By comparing Example 11 with Comparative Example 3, it is evident thatwith the process using the tertiary amine of the present invention, theobtainable optically active ally compound has a high optical purity.

By comparing Examples 6 to 9 with Comparative Examples 5, it is evidentthat with the process using the tertiary amine of the present invention,the reaction system does not become gelled, and the obtainable opticallyactive ally compound has a high optical purity.

INDUSTRIAL APPLICABILITY

It is possible to use the present invention as a novel process forproducing an optically active allyl compound which is useful as anintermediate raw material for e.g. pharmaceutical products.

The entire disclosure of Japanese Patent Application No. 2006-030964filed on Feb. 8, 2006 including specification, claims and summary isincorporated herein by reference in its entirety.

1. A process for producing an optically active allyl compound of theformula (4):

(wherein “*” represents an asymmetric carbon atom), which comprisesreacting an allyloxy compound of the formula

(wherein R¹ is a C₁₋₆ alkyl group or a C₁₋₆ alkoxyl group, and each ofR², R³, R⁴, R⁵ and R⁶ independently is a C₁₋₆ alkyl group which may belinear, branched or cyclic, a hydrogen atom or a C₆₋₁₂ aromatic group,provided that R² and R⁶ may be located in the same ring) with ahydrogenated compound of the formula (3):

(wherein X is a carbon atom, an oxygen atom, a sulfur atom or a nitrogenatom, and each of R⁸, R⁹ and R¹⁰ independently is a C₁₋₂₄ alkyl groupwhich may be linear, branched or cyclic, a C₁₋₂₄ alkylcarbonyl groupwhich may be branched or cyclic, a C₁₋₂₄ alkoxycarbonyl group which maybe branched or cyclic, a hydrogen atom, a halogen atom or a C₆₋₁₀aromatic group, or two of R⁸, R⁹ and R¹⁰ may together form a ringcontaining one or two carbonyl groups), in the presence of a palladiumcompound and an optically active phosphine ligand of the formula (2):

(wherein each of Ar¹, Ar², Ar³ and Ar⁴ independently is a C₆₋₁₀ aromaticgroup, and R⁷ is a structure having at least one asymmetric center oraxial chirality), wherein a tertiary amine of the formula (5):

(wherein each of R¹¹, R¹² and R¹³ independently is a C₂₋₁₂ aliphaticgroup or a C₂₋₁₂ substituted aliphatic group, which may be linear,branched or cyclic, or a C₆₋₁₀ aromatic group or a C₆₋₁₀ substitutedaromatic group) is present in the above reaction system.
 2. The processaccording to claim 1, wherein the optically active phosphine ligand is acompound of the formula (6):


3. The process according to claim 1, wherein the optically activephosphine ligand is a compound of the formula (7):


4. The process according to claim 1, wherein the allyloxy compound iscyclopentenyl acetate of the formula (8):


5. The process according to claim 1, wherein the allyloxy compound is acompound of the formula (9):


6. The process according to claim 1, wherein the tertiary amine istri-n-propylamine.
 7. The process according to claim 1, wherein thetertiary amine is tri-n-octylamine.
 8. The process according to claim 1,wherein the tertiary amine is diisopropylethylamine.
 9. The processaccording to claim 4, wherein the hydrogenated compound is a compound ofthe formula (10):


10. The process according to claim 1, wherein the hydrogenated compoundhas a pKa of at most 16 in water.